The long range goal of this research is to understand the cellular mechanisms by which associations are made during learning. The marine snail Aplysia provides an advantageous model system for the analysis of simple forms of learning because of its nervous system with neurons that are relatively few in number, large and uniquely identifiable. Classical conditioning of the defensive withdrawal reflex of Aplysia resembles conditioning in vertebrates in a number of respects. An associative form of synaptic plasticity, activity-dependent synaptic facilitation, which occurs within single sensory neurons in the conditioned stimulus pathway, plays an important role in the associative changes produced by conditioning. The specific aim of this proposed study is to analyze how spike activity in a sensory neuron, which is triggered by the conditioned stimulus, enhances the cell's synaptic facilitation response to modulatory input that produced during training by the unconditioned stimulus. The enzyme adenylate cyclase in the sensory neuron has been shown to provide a molecular site of associative interaction between Ca2+ influx, which accompanies the cell's own spike activity, and modulatory transmitter. Neurophysiological studies on intact sensory neurons will be carried out to critically evaluate the role of adenylate cyclase in activity-dependent facilitation. Biochemical studies will attempt to analyze how the two inputs, Ca2+ influx and modulatory transmitter, interact in activating the cyclase. Activity-dependent facilitation has some striking similarities with associative long-term synaptic potentiation in mammalian hippocampus and with activity-dependent tuning of synaptic connections that occurs in the developing vertebrate visual system. A thorough understanding of this form of activity- dependent synaptic plasticity may aid in our understanding of other types of activity-dependent neural changes during learning and during development.